Placental Macrophages Demonstrate Sex-Specific Response to Intrauterine Inflammation and May Serve as a Marker of Perinatal Neuroinflammation. (September 2021)

• Record Type: Journal Article
• Authors: Na, Quan; Chudnovets, Anna; Liu, Jin; Lee, Ji Yeon; Dong, Jie; Shin, Na; Elsayed, Nada; Lei, Jun; Burd, Irina
• Is Part Of: Journal of reproductive immunology. Volume 147(2021)
• Publication Date: 2021-09
• Subjects: Plaental -- macrophages -- microglia -- intrauterine inflammation -- fetal brain injury -- preterm birth; Reproduction -- Immunological aspects -- Periodicals; Immunology -- Periodicals; Allergy and Immunology -- Periodicals; Reproduction -- Periodicals; Reproduction -- Immunologie -- Périodiques; Immunologie -- Périodiques; Immunology; Reproduction -- Immunological aspects; Periodicals; Electronic journals; Electronic journals; 615.766
• DOI: 10.1016/j.jri.2021.103360
• Languages: English
• ISSNs: 0165-0378

Abstract

Highlights: The polarization of placental macrophages changes following immune activation in placenta exposed to intrauterine inflammation. A strong correlation exists between placental macrophage infiltration following intrauterine inflammation and microglia activation in the fetal brain. Hofbauer cell activation following intrauterine inflammation leads to a sex-specific effect whereby males were more vulnerable to early inflammatory insult. Abstract: Preterm birth (PTB) is considered to be one of the most frequent causes of neonatal death. Prompt and effective measures to predict adverse fetal outcome following PTB are urgently needed. Placenta macrophages are a critical immune cell population during pregnancy, phenotypically divided into M1 and M2 subsets. An established mouse model of intrauterine inflammation (IUI) was applied. Placenta (labyrinth) and corresponding fetal brain were harvested within 24 hours post injection (hpi). Flow cytometry, Western blot, real-time qPCR, and regular histology were utilized to examine the cytokines, macrophage polarization, and sex-specificity. Placental exposure to LPS led to significantly reduced labyrinth thickness compared to PBS-exposed controls as early as 3 hpi, accompanied by apoptosis and necrosis. Pro-inflammatory M1 markers, Il-1β, and iNOS, and anti-inflammatory M2 marker Il-10 increased significantly in placentas exposed to IUI. Analysis of flow cytometry revealed that fetal macrophages (Hofbauer cell, HBCs) were mostly M1-like and that maternal inter-labyrinth macrophages (MIM) were M2-like in their features in IUI. Male fetuses displayed significantly decreased M2-like features in HBCs at 3 and 6 hpi, while female fetuses showed significant increase in M2-like features in MIM at 3 and 6 hpi. Furthermore, there was a significant correlation between the frequency of HBCs and corresponding microglial marker expression at 3 and 6 hpi. Placental macrophages demonstrated sex-specific features in response to IUI. Specifically, HBCs may be a potential biomarker for fetal brain injury at preterm birth.